Structural basis of menaquinone reduction by succinate dehydrogenase from Chloroflexus aurantiacus

Xin Zhang, Jingyi Wu, Jiamao Wang, Huimin He, Aokun Liu, Xin Hong, Yuanyi Yu, Xinkai Pei, Xianjie Fang, Yueyong Xin (), Lu Yu (), Changlin Tian () and Xiaoling Xu ()
Additional contact information
Xin Zhang: Hangzhou Normal University, Zhejiang Key Laboratory of Medical Epigenetics
Jingyi Wu: Hangzhou Normal University, Zhejiang Key Laboratory of Medical Epigenetics
Jiamao Wang: Hangzhou Normal University, Zhejiang Key Laboratory of Medical Epigenetics
Huimin He: Hangzhou Normal University, Photosynthesis Research Center, College of Life and Environmental Sciences
Aokun Liu: University of Science and Technology of China, Division of Life Sciences and Medicine
Xin Hong: Hangzhou Normal University, Zhejiang Key Laboratory of Medical Epigenetics
Yuanyi Yu: Hangzhou Normal University, Zhejiang Key Laboratory of Medical Epigenetics
Xinkai Pei: Hangzhou Normal University, Zhejiang Key Laboratory of Medical Epigenetics
Xianjie Fang: Hangzhou Normal University, Zhejiang Key Laboratory of Organosilicon Material Technology
Yueyong Xin: Hangzhou Normal University, Photosynthesis Research Center, College of Life and Environmental Sciences
Lu Yu: University of Science and Technology of China, Division of Life Sciences and Medicine
Changlin Tian: University of Science and Technology of China, Division of Life Sciences and Medicine
Xiaoling Xu: Hangzhou Normal University, Zhejiang Key Laboratory of Medical Epigenetics

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Succinate: menaquinone oxidoreductase (SQR) couples the oxidation of succinate with the reduction of menaquinone (MK) as part of the TCA cycle and the aerobic respiratory chain in MK-containing bacteria and archaea. Despite its significance, questions persist regarding the electron and proton transfer mechanisms that drive the endergonic MK reduction by succinate. In this study, we determine cryo-EM structures of succinate dehydrogenase (SDH) from Chloroflexus aurantiacus (CaSDH), a facultative filamentous anoxygenic phototroph (FAP) that forms one of the earliest branches of photosynthetic bacteria. The structures of trimeric CaSDH, resolved in both apo- and MK-bound forms, reveal a single membrane-anchoring subunit containing two b-type hemes, a canonical QP site, and a QD site with atypical location, configuration and specificity, each bound to MK molecules. Using structural analysis, EPR, and enzymatic assays, we uncover electron transfer pathways connecting succinate oxidation to MK reduction at the QP and QD sites. These findings provide structural insights into the electron and proton transfer mechanisms of MK-dependent diheme SQRs and establish a foundation for structure-based inhibitor design and antibacterial drug development targeting these enzymes.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65828-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65828-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65828-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().